Syringe adapter with a driver for agitation of the syringe content

ABSTRACT

Administration by injection or infusion to patients of an injectable liquid for diagnostic or therapeutic purposes is provided by a syringe adapter connectable with an automatic syringe pump and a syringe containing contents to be dispensed. The syringe adapter includes an adapter body receivable by the syringe pump, a syringe retainer for retaining the syringe, and a syringe driver for agitating the contents of the syringe. More particularly the invention relates to an adapter connectable with a syringe pump and methods for delivery of an injectable liquid using such adapter. By connecting an adapter according to the invention to a syringe and a syringe pump, rotation of the syringe is achieved and homogeneity of the injectable is preserved. Particularly, the injectable liquid is an ultrasound contrast agent comprising an aqueous dispersion of gas-filled microbubbles or of particulate matter.

FIELD OF THE INVENTION

The present invention relates to devices for administration by injectionor infusion of liquid compositions for diagnostic or therapeuticpurposes. More particularly the present invention is directed to anadapter for a syringe pump used to dispense the contents of a syringemaintaining a homogeneous solution during dispensing.

DESCRIPTION OF RELATED ART

In a number of medical procedures, it Is desirable to continuouslyinject a multi-component medium to a patient. An example of such amedical procedure is ultrasound imaging. For ultrasound imaging the mostcommon contrast media comprises gas-containing microbubbles dispersed inan aqueous carrier. A problem with the continuous infusion of suchcontrast media arises from the tendency of microbubbles to float, sincethis may lead to inhomogeneities forming within vessels such aspower-driven syringes which may be used to administer the contrastagent. This may, for example, lead to an increase in microbubbleconcentration in the upper part of such a vessel and/or to changes insize distribution occurring at various points within the vessel aslarger microbubbles float more rapidly than smaller microbubbles.

Power injectors for continuous controllable delivering of diagnostic andtherapeutic injectable liquids are well known. Typically such apparatusinclude an automatic syringe pump for coupling to a syringe containingan injectable liquid. Such syringe further has a plunger or pistonmovable within the barrel of the syringe to expel the liquid through atip thereof. The automatic syringe pump typically has asyringe-receiving unit, adapted to hold the syringe, and anelectromechanical arrangement organized to push the plunger of thesyringe at a desired rate. The mode and rate of injection or infusion ishence accurately controlled. Compared to hand injection, automaticsyringe pumps have the benefit of maintaining a consistent flow over along time, thereby providing a consistent amount of the injectableliquid, such as a contrast media, In the blood stream.

The available syringe pumps on the market have, however, no control ofthe homogeneity of the injectable liquid stored in the syringe barrelduring the course of administration. When the injectable liquid is adispersion of particles that tend to settle, float, coalesce orsegregate, such as e.g. an ultrasound contrast agent, it is desirable tokeep the contents of the syringe homogeneous during administration. Asautomatic syringe pumps are frequently used in infusion or injections,and as such equipment is available in most hospitals, it is alsodesirable to enable use of such pumps for administration of aninjectable liquid wherein preservation of homogeneity is needed. Thepresent method and devices give an effective solution to this problem.

Some methods and devices for maintaining a homogeneous solution duringadministration have been described earlier. WO 99/27981 describes anautomatic injection system and a method for its use. The injectionsystem includes a syringe containing a dispersion and this dispersion issubjected to a rotation or rocking motion in order to maintain ahomogeneous dispersion. This patent application further describes aninjection system comprising a syringe, automatic electromechanical powermeans, and means for agitating the dispersion in the syringe, such ase.g. a set of rollers. The injection system includes a pump suited forrotation of an integrated syringe.

WO 00/53242 describes devices, systems and methods for dispensing amulti-component medium. A system described comprises a container to holdthe medium, a pressurizing device, such as a pump, and an agitationmechanism or device to maintain the components of the medium in a mixedstate. Several ways of achieving agitation are described, e.g. rotationof a storage volume.

WO 00/12157 and WO 00/12158 describe syringes and pumps incorporating anagitation device, such as a ball, respectively a magnetic agitationdevice and a mechanical agitation device. WO 00/12158 further describesthat the system can include accessories encompassing devices physicallyconnected to a pump and assume the role of moving the entire pump orparts thereof in such a way that the syringe changes position. Examplesof such accessories are a table for the pump executing a wobblingmovement and a motor-drive shaft.

Each of the above-described systems therefore provide agitation meansintegrated into the syringe pump or a syringe. There is still a need inthe art, however, for providing an agitation capability to alinear-stroke automatic syringe pump both before and duringadministration of the injectable liquid.

SUMMARY OF THE INVENTION

In view of the needs of the art the present invention provides a syringeadapter connectable with an automatic syringe pump and a syringecontaining an injectable liquid to be dispensed. The adapter comprisesmeans for agitating the injectable liquid of the syringe.

A syringe is defined as a unit that may contain a liquid composition forinjection or infusion. The syringe mainly comprises a barrel, a nozzleand a plunger. The term syringe also encompasses so called cartridgesadapted to be connected to syringe pumps. Such cartridges include aplunger, but not necessarily a plunger rod.

A syringe pump is defined as an apparatus used in automatic andcontrolled administration of a liquid composition from a syringe. Suchpumps are also called infusion pumps, power injectors and injectorsystems.

Furthermore, the present invention provides apparatus and methods fordelivery of an injectable liquid, such as an ultrasound contrast agent,to a patient. Particularly the invention provides methods and devicesfor securing homogeneity of the liquid during administration, such asduring an infusion procedure. The invention gives a method and meanswhereby the injectable liquid is kept under sufficient agitation so asparticles in the composition do not settle, segregate, float oragglomerate undesirably.

In the present invention the mixing device is an adapter which receivesa syringe. The adapter itself is received by an automatic syringe pump.The adapter of the present invention is suitable for use with availablemarketed pumps and with conventional syringes so as to preserve thehomogeneity of the liquid to be administered. The great advantage of theadapter of the invention is that this allows for use of standard syringepumps available at the market. Additionally it is easy to use andvalidate.

By connecting the adapter to a pump and a syringe, rotation of thesyringe is achieved and the composition in the syringe is sufficientlyagitated to keep the components of the injectable liquid in a mixedstate during administration. Mechanical agitation is provided to theextent that is sufficient to keep the composition homogeneous butinsufficient to break or damage the particles in the composition.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 illustrates an automatic syringe pump of the prior art.

FIG. 2 a illustrates a first adapter according to the present invention.

FIG. 2 b illustrates the adapter of FIG. 2 a further indicating thesyringe driver.

FIG. 3 illustrates the adapter of FIG. 2 placed in the automatic syringepump of FIG. 1.

FIGS. 4 and 5 illustrate the adapter of FIG. 2 placed in an automaticsyringe pump and how to connect the adapter to a syringe.

FIG. 6 illustrates the operation of an apparatus comprising a pump, asyringe and an adapter of FIG. 2.

FIG. 7 illustrates a second embodiment of an adapter according to thepresent invention.

FIG. 8 illustrates a third embodiment of an adapter according to thepresent invention.

FIG. 9 illustrates the adapter of FIG. 8 placed in a pump of FIG. 1 andconnected to a syringe.

DETAILED DESCRIPTION OF THE INVENTION

A first embodiment of the present invention is an adapter connectablewith an automatic syringe pump and/or a syringe, the syringe containingcontents to be dispensed, said adapter comprising means for agitatingthe content of the syringe.

The adapter is detachably connectable to standard syringe pumps andsyringes. That is, the adapter can be connected, joined, linked,fastened or coupled to, and de-tached from, an automatic syringe pumpand/or a syringe. The adapter comprises an adapter body receivable by asyringe-receiving unit of the syringe pump. The adapter furthercomprises means for agitating the syringe by primary rotationalmovements.

Various types of syringe pumps are currently available on the marked.Briefly stated, such pumps generally comprise a syringe receiving-unit,a dispense shaft or drive head, a motor and electronics to drive thedispense shaft controllably against a syringe plunger or piston, and acontrol keyboard. Many pumps also have a size-reading unit or in anotherway has the capability of reading the size of the syringe attached. Whenplacing a syringe in the syringe receiving-unit of the pump thissize-reading-unit registers the diameter of the syringe placed in thepump. Based on this size-reading the syringe dimensions are calculatedgiving the correct injection rate when set to operate. The pumps aredesigned to comply with standard syringe sizes.

To ensure compatibility with existing pumps the adapter of the inventionincludes a portion having the same or similar geometry as a syringe. Theadapter is designed to have partly the same geometry as a syringe inorder to comply with the syringe receiving-unit, e.g. a syringe cradle,of the pump. Desirably the adapter also has geometry complying with anysize-reading-unit of the pump. When placing the adapter in thesyringe-receiving-unit of the pump and the syringe size-reading-unit isclosed the pump will select the correct syringe size, based on thereading of the adapter dimensions, and thereby giving the correctinjection rates when set to operate.

The adapter at least comprises an adapter body, a syringe retainer, anda syringe driver for agitating the injectable contents of the syringe.

To ensure compliance with the pump the adapter body comprises desirablyan elongate cylindrically shaped housing portion receivable in thesyringe pump. Desirably, this body has a circular cross-section,resembling the barrel of a syringe. Most desirably, to ensure maximumcompatibility with existing pumps used in hospitals the adapter has atleast partly the same shape and size as a 50-ml syringe. When theadapter is placed in a pump, the pump therefore “believes” a syringe hasbeen placed in the pump, and it calculates the right rate ofadministration, based on the dimensions of the adapter. A sizereadable-unit of the adapter is designed to comply with anysize-reading-unit of the pump. This unit desirably has substantially thesame cross-section as the barrel of the syringe to be used. Mostdesirably the size-readable unit of the adapter has the diameter as thebarrel of a 20-ml or 10-ml syringe.

The syringe driver comprises means for agitating the content of thesyringe. Desirebly the adapter body further includes such means forproviding rotation of the syringe retainer. These means for rotationcould comprise a motor, electronics, means for communicating with theuser (display, buttons etc.) and converters. A power source likebatteries, optionally chargeable, mains to the net, or a mechanicalenergy source may be included. Rotation can be achieved e.g. with a beltor wheel actuated by a motor of some kind. The motor is desirablyintegrated inside the adapter body. Optionally, any size-readable unitcan eiher be integrated as part of the adapter housing or could be aseparate unit connected with the housing.

The syringe retainer of the adapter is designed to hold and rotate thesyringe. Energy is transferred from the motor in the adapter body to thesyringe retainer and motor driven rotation of the syringe is enabled.There may hence be a torsion energy transfer from the motor to thesyringe retainer. The rotational part of the retainer may comprise aswivel connector, a ball-bearing rotating arrangement that allowsrotating while being fixed, a needle bearing system, a sleeve bearingsystem, rolling bearings or others, and holding means such as jaws or aclamp. The syringe retainer comprises both holding and rotational means.The syringe retainer may include a snap/quick fit system, a splint,barbs, threaded connections or other locking mechanisms for connectingthe syringe to the adapter. Preferably the syringe retainer includes aninsertion aperture, through which a syringe may be threaded. Theretainer should then comprise a syringe ring which further comprisessyringe retaining means extending about the insertion aperture forengaging and retaining the syringe. Moreover, the syringe retainer maybe designed to accommodate the flanges of a syringe to form a lockablerotateable holder. A syringe may then be inserted by threading itthrough the insertion aperture of the adapter, rotating the syringe 90degrees and reversing the direction of insertion. The flanges of thesyringe will then engage the rotating part of the adapter.Alternatively, the syringe may be threaded through the insertionaperture and locked directly in the retaining means without having torotate it 90 degrees. The syringe retainer will then engage and retainthe syringe after direct insertion of the syringe. The attachment of aguide piston, as later described, will also support holding the syringein place in the syringe retainer. The syringe ring is preferablyexchangeable.

The syringe driver means enables agitation of the content of thesyringe. The syringe driver preferably comprises a motor and drivemeans, preferably positioned within the adapter body as described above.The drive means, transferring power from the motor to the syringe, maye.g. comprise drive belts, toothed wheels, axles, shafts, chains orstraps. Preferably the drive means comprises a drive belt engaging amoving portion of the motor and the syringe retainer, such as thesyringe ring in the insertion aperture of the syringe retainer. Thesyringe driver causes the syringe ring to reciprocally rotate about theinsertion aperture.

A further aspect of the invention is a plunger-pressure-unit of theadapter which is designed to transfer the injection movement from thedrive head of the pump to the plunger of a syringe held by the syringeretainer. The dispense shaft of the pump can hence act on thisplunger-pressure-unit, to effect movement of the pump to the syringeplunger. The plunger-pressure-unit hence acts as an extension to thedrive head. The plunger-pressure-unit may simply consist of a guidepiston. The drive head of the pump may hence act directly on this guidepiston transferring movement from the pump to a syringe plunger. Theadapter body then defines a guide piston opening and an elongate guidepiston passageway in fluid communication with the guided piston openingfor slidably receiving the guide piston between a first and secondposition. However, the geometry and dimensions of some drive heads maybe sufficient to directly act upon a plunger of the syringe held by anadapter of the present invention, making such plunger-pressure-unitredundant. Alternatively, the plunger-pressure-unit may comprise anextension arm in addition to the guide piston. The extension armpreferably includes a free end in movable spaced registry with thesyringe retainer. Preferably, the extension arm is pivotally mounted tothe guide piston. Further, the extension arm may support a dispense rodfor engaging the syringe plunger. Ideally, the dispense rod should beable to either rotate freely or with as little friction as possible withthe syringe plunger. Preferably, the guide piston is adopted to moveslideably, with as little friction as possible.

The different parts of the adapter may be arranged in alternative ways.The adapter body, the syringe retainer, and the guide piston may all bepositioned substantially in-line. When in-line, desirably the adapter isshaped as a syringe having a substantially elongate cylindrically shapedhousing, a guide piston extending from one end of the housing, goinggenerally through the cylindrical housing, and a syringe retainer,forming the other end of the cylindrical. A syringe can hence be mountedto one end of the elongate body. When placing a syringe in the retainerthe cylindrical housing, the guide piston and the syringe will bepositioned substantially in-line. Alternatively, the adapter is designedsuch that the syringe retainer holds the syringe substantially inparallel with the cylindrical housing. Preferably, the syringe retaineris offset from the adapter body.

A syringe placed in the adapter is subjected to a rotational agitation,continuous or discontinuous, optionally altering the rotation directionand desirably the speed of the rotation. Generally, when a syringecontaining a stationary fluid is rotated a certain angle around itscentral longitudinal axis, the fluid volume inside is displaced in apredictable manner. When the motion is reversed by moving the cylinderback to its original angular position, the fluid will eventually alsomove back again to its original position, and sufficient agitation hasnot been achieved. The adapter of the invention desirably imparts arotation around the longitudinal central axis of the syringe. Therotation may however also take place outside the central axis, turningthe syringe around a line outside the central longitudinal axis. Themovement may also take place in the longitudinal direction of thesyringe.

The movement may be continuous or discontinuous. However, the adapterdesirably subjects the syringe to an oscillating rotation making anasymmetric pattern. The oscillating rotation may be performed byalternately rotating the syringe at a certain angle In one direction andthen reciprocally in the opposite direction so as to prevent a harmonicoscillation of the dispensable fluid. Alternatively, the syringe may berotated at different angles in the opposite directions. The mostpreferable way of achieving an asymmetric rotation is by alternatelyrotate the syringe in opposite directions, around its longitudinalcentral axis, wherein the speed of rotation differs in the twodirections. Alternatively, asymmetric rotation may be achieved byrotating at set angles but at varying speed of rotation. If the angularspeed of rotation is different when the reverse rotation is performed,there will be a small net displacement of the fluid when returning tothe original position. This is caused by non-linearities in the viscousbehavior of the fluid, and possibly also turbulence if the angularacceleration is high enough. An oscillating rotational shaking of asyringe in this manner will hence cause a long-term net rotation of thefluid inside the syringe. A short angle back-and-forth rotationalshaking has a substantial advantage, since any tubing from the syringeto the patient will not become twisted. Although the angular excursionsmight be quite small, there will be a complete shaking, since acontinuous circulation flow pattern is generated in the syringe. About1-6 rotations should however not be a problem for the tube.

FIG. 1 illustrates an automatic syringe pump 1 of the prior art. Similarpumps are available on the market, such as for instance a FreseniusDPSIS. A syringe with a composition for delivery may be connected to orplaced in the pump, and the pump enables controllable delivery of thecompositions to a patient. An adapter of the invention may be used withsuch pump. The pump of FIG. 1 has a pump housing 2. The pump further hasa syringe-receiving-unit 3. This unit is designed to receive a syringe,and will typically have a substantially half-cylindrical shape, forminga cradle 3 a. In combination with the syringe-receiving-unit 3 there isa syringe size-reading-unit 4. When placing a syringe in the syringereceiving-unit 3 this part of the pump reads the size of the syringeinstalled, usually based on the diameter of the syringe. Thesize-reading-unit 4 will typically comprise a clasp 4 a that can pivotbetween an opened position allowing access to cradle 3 a and a closedposition in spaced registry with cradle 3 a so as to retain a syringetherein. The pump further comprises an elongatelongitudinally-displaceable dispense shaft 5. When placing a syringe inthe pump the dispense shaft 5 engages and moves the plunger rod of thesyringe. The housing 2 includes electromechanical arrangement enabling adriving of the dispense arm 5 of the pump towards the syringe at adesired rate so as to provide controlled dispensing of the contents ofthe syringe. The dispense arm 5 supports a pump drive head 6 at one endwhich itself may support drive release and anti-siphon controls 6 a.Drive head 6 engages the piston shaft of a common syringe or dispensesyringe positioned in cradle 3 a so as to cause the contents of thesyringe to dispense as dispense arm 5 carries drive head 6 towards thesyringe. The pump should further have a control panel 7 for assisting anoperator.

FIG. 2 a illustrates a first example of an adapter 9 according to thepresent invention. The adapter 9 is compatible with the pump 1 ofFIG. 1. The adapter 9 includes an elongate adapter body, or housing, 10having geometry complying with the syringe receiving-unit 3 of the pump1 in FIG. 1. Adapter 9 also includes a syringe retainer 12 forretentively engaging a syringe having contents to be dispensed. Asyringe driver mechanism is also provided, described hereinbelow, foragitating the contents of the syringe. Housing 10 is typically formed ofa suitably rigid plastic material and desirably includes a substantiallyelongated cylindrical portion 40, resembling the barrel of a syringe.Housing 10 includes a size readable-unit 11 designed to fit within thesize-reading-unit 4 of the pump 1. Size readable-unit 11 comprises aneck 42 and an annular shoulder 44 which simulate the size and shape ofthe base end of a syringe or dispense syringe.

Adapter 9 further includes a syringe retainer 12 at a free end of aholding arm 13 extending substantially transversely to housing 10.Syringe retainer 12 defines an annular track within which a syringe ring14 may rotate. A syringe may be positioned in syringe retainer 12 androtated with syringe ring 14, as shown in FIG. 4. Syringe ring 14defines an insertion aperture 50 into which a syringe having contents tobe dispensed may be inserted and retained. Syringe ring 14 desirablyincludes a number of retaining arms 52 extending towards insertionaperture 50 for retentively engaging an inserted syringe. Retaining arms52 define opposed first and second open notches 53 and 55 for allowingthe flanges of a syringe to pass there through. Retaining arms 52further define there between opposed first and second closedflange-receiving notches 54 and 56 into which the flanges of a syringemay be retentively engaged.

Annular shoulder 44 defines a guide opening 46 in fluid communicationwith a guide piston passageway 48, shown by phantom lines, defined byhousing 10. Passageway 48 slidingly accommodates a guide piston 16therein. A free end of guide piston 16 supports an extension arm 15which engages the drive head 6 of syringe pump 1. Extension arm 15extends substantially transversely to guide piston 16 and desirablysupports a dispense rod 17 at a free end 15 a in spaced registry withinsertion aperture 50. Dispense rod 17 may be rotationally supported onextension arm 15 by an axle 18. Alternatively, dispense rod may be fixedwith respect to extension arm 15. Movement of extension arm 15 and guidepiston 16 is further illustrated in FIG. 5.

The adapter 9 further includes means for imparting rotational energy tothe syringe ring 14, as shown by phantom lines in FIG. 2 b. Adapter 9includes an electric motor 56 which rotates a drive shaft 58. One freeend of drive shaft supports a drive belt 60. Drive belt 60 extendsthrough an open interior portion of holder 13 and in annular track 49about syringe ring 14. Motor 56 may rotate continuously in a singledirection as well as in a reciprocating motion so as to causes a syringeheld by syringe retainer 12 to be agitated, thereby preserving thehomogeneity of the contents of the syringe. Motor 56 desirably urgessyringe ring 14 to reciprocatingly rotate through about ninety degreearcs so as to impart a reciprocating rotation of the inserted syringe.Motion of motor 56 is desirably directed by controller circuitry 62which operates according to operator selected inputs at control panel64. Control panel 64 desirably provides an operator to, at a minimum,select a pre-programmed routine for rotation of syringe ring 14, such asthe speed, direction, and amount of rotation. On-off controls allow theoperator to commence and terminate agitation of the inserted syringe.

FIG. 3 illustrates the adapter 9 of FIG. 2 placed in the automaticsyringe pump 1 of FIG. 1. Cylindrical portion 40 of housing 10 of theadapter is positioned in cradle 3 a of syringe receiving-unit 3.Extension arm 15 and dispense rod 17 are shown positioned towards theinsertion aperture 50 of adapter 9. When having positioned the adapter 9in the syringe receiving-unit 3, the clasp 4 a of size-reading-unit 4 isin the closed position about neck 42 of size readable unit 11. The pumpmay correlate the outer dimensions of neck 42 with a stored softwareprogram, thereby giving the correct injection rates when set to operate.

FIG. 4 illustrates the adapter 9 positioned in an pump 1 while alsoaccommodating a syringe 20. Syringe 20 is a typical syringe as known inthe art and includes an elongate barrel 21, flanges 22transversely-extending from a base of barrel 21, a plunger 23, and aplunger rod 24. Syringe 20 is optionally connected to a tubing 25 at thesyringe nozzle 26. The filled syringe 20 is inserted, plunger end first(as shown by arrow A), through insertion aperture 50 of syringe ring 14desirably. The syringe ring 14 of syringe retainer 12 defines a patterncomplying with the flanges 22 of the syringe to allow the flanges toclear through aperture 50. After having Inserted syringe 20 throughsyringe ring 14, the syringe 20 is rotated 90 degrees (depicted by arrowB) and the direction of insertion is reversed (depicted by arrow C) toretain syringe 20 within syringe ring 14. The flanges 22 of the syringewill engage with the retaining arms 52 of syringe ring 14 therebylocking syringe 20 in the syringe retainer 12. The syringe 20 nowextends generally in parallel to adapter housing 10.

FIG. 5 further illustrates the cooperation between drive head 6 of thesyringe pump, extension arm 15 of the adapter, and syringe plunger rod24 so as to dispense the contents of syringe 20. The dispense rod 17 ofextension arm 15 may be manually positioned in abutting engagement withthe free end of plunger rod 24 of syringe 20. Pump drive head 6 is movedinto abutting engagement with extension arm 15. The entire dispenseapparatus, comprising pump 1, syringe 20, and adapter 9 is now ready foroperation, as is further illustrated in FIG. 6. Movement of drive head 6urges extension arm 15 and, hence, plunger rod 24 in a dispensingdirection which discharges the contents of syringe 20 through nozzle 26.Pump 1 may be set to run with injection rates as per instructions forthe product to be injected or infused. As pump 1 cannot distinguishbetween adapter 9 and syringe 20, all features, such as alarms,occlusion stop etc. in the pump will still be active. During injectionsyringe 20 will have the set longitudinal dispense rate (denoted byarrows D,E, and F) ensured by the pump 1, while the optimum sequence ofalternating rotation (denoted by arrow G) of the syringe 20 is ensuredby adapter 9.

FIG. 7 illustrates a second alternative of an adapter 30 according tothe invention connected to a syringe 20. This adapter 30 has the samemain parts as the adapter 9 of FIG. 2, with like numerals denoting likecomponents; a housing 110, a syringe size readable-unit 111, anextension arm 115 and a syringe retainer 112. In this alternative,however, syringe size readable-unit 111 forms an integrated part of thehousing 110. Desirably, syringe size readable-unit 111 includes asubstantially circular cross-section but it may include a substantiallyplanar portion 111 a so as to provide an outer dimension shaped to mimicthe dimensions of a particular-sized syringe to the size-reading-unit 4of pump 1. Further, syringe retainer 112 is directly mounted to housing110, without an extending holder arm. The extension arm 115 is supportedby elongate guide piston 116 and supports dispense rod 117. Member 117is an elongate member especially suited for dispensing the contents fromdispense syringes which, while including a slidable piston, lack aplunger rod. Member 117 thereby acts as the plunger rod to move theslidable piston. Dispense rod 117 further supports a swivel 131 at afree end thereof in spaced registry with insertion aperture 150. Swivel131 allows the plunger rod 24 of a syringe 20 to more freely rotate withsyringe barrel 21. The present invention contemplates that extension arm115 may be pivotally mounted at an axle 161 so as allow dispense rod tobe movable about arrow H between opposed positions in and out ofregistry with insertion aperture 150. Axle 161 thereby allows a syringeto be loaded through insertion aperture 150 nozzle end first. A moredetailed sketch of the retainer 112 is shown in a separate extract inFIG. 7. An electric motor 156 is in connection with a rotating shaft 158In driving engagement of a syringe ring 114. Syringe ring 114 rotateswithin an annular track 149 defined by syringe retainer 112. The syringering 114 and the drive shafts 158 are connected by several toothedwheels 160 to enhance driving engagement therebetween.

FIGS. 8 and 9 illustrate another adapter 35 of the present invention,with like numerals denoting like components to the herein abovedescribed embodiments. Adapter 35 is shown connected to a syringe 20.The adapter 35 comprises an elongate substantially cylindrical housing210, a size readable-unit 211 by which adapter 35 is retained by a pump1, an elongate guide piston 216 and a syringe retainer 212. Syringe 20is positioned by adapter 35 to be substantially in-line with housing210. The housing 210 generally resembles a syringe barrel having asubstantially cylindrical shape.

The adapter 35 includes a motor 256, drive shaft 258 and controlcircuitry, such as a battery, 262, transferring energy to the syringering 214 which forms a part of the syringe retainer 212.

Adapter 35 further includes an elongate guide piston 216 which islongitudinally movable under the urging of drive head 6 of pump 1.Housing 210 further defines an elongate guide piston passageway 248 foraccommodating guide piston 216 therethrough. Guide piston 216 supports asyringe plunger engagement member 215 at first end 216. The member 215is therefore able to urge the syringe plunger rod of syringe 20 towardsnozzle 26 and thereby provide for dispensement of the syringe contents.

FIG. 9 illustrates an apparatus comprising the adapter 35 of FIG. 8loaded in pump 1 and connected to a syringe 20. When adapter 35 ispositioned in the syringe-receiving-unit 3 of the pump 1, clasp 4 a ofsyringe-size-reading unit 4 is closed, thereby holding adapter 35 by thesyringe-size-readable-unit 211. When having connected a syringe 20 tothe syringe retainer 212 and the pump drive head 6 attaches the guidepiston 216 the apparatus is ready for operation. Rate and mode ofinjection will be ensured by the pump, pushing the guide piston 216 at adesired rate, while the desired rotational agitation is ensured by theadapter 35.

Another embodiment of the invention is an injection apparatus employingan adapter of the present invention. Such apparatus may be used foradministration of an injectable liquid and comprises an automaticsyringe pump and an adapter of the invention, and optionally a syringe.Desirably, such apparatus is used for injection or infusion of adispersion of microparticles homogeneously distributed in a carrierliquid. The adapter includes means for rotating the syringe to obtain auniform distribution of the liquid composition in the syringe. Theapparatus may further comprise a tube connected to the syringe nozzlefor transferring the composition to a patient. Optionally the apparatusmay comprise means for admixture of the composition of the syringe witha flushing medium prior to administration to a subject. Such means maysimply comprise a three-way connector, e.g. a T-piece, a Y-piece or atap such as a three way stopcock connected to a tubing from the syringeand a flushing medium reservoir.

Yet another embodiment of the invention is use of the adapter and theapparatus as herein described. Accordingly, a method of administering aninjectable liquid composition using such apparatus is encompassed.Desirably, a method of administering is by injection or infusion of adispersion of microparticles homogeneously distributed in a liquidcarrier by an apparatus comprising a pump, a syringe comprising thedispersion and an adapter, wherein the adapter comprises means forrotating the syringe to obtain a uniform distribution in said syringe.Another aspect of this embodiment is a method of agitating a compositionto be mixed or to be held homogeneous, using the adapter or theapparatus of the invention.

The adapter, method and apparatus of the invention may be used foradministration of different liquid compositions to patients, humanbeings or animals. The compositions may be for therapeutic or diagnosticpurposes. The apparatus may be used for administration of anycomposition comprising multi-component fluids wherein the components arenot totally miscible and there is a tendency for the components toseparate over time. Such composition may comprise particles that tend tosettle, float, coalesce or segregate. The apparatus and method of theinvention is particularly useful for administration, such as injectionor infusion, of dynamic (i.e. gravity segregating) particulatedispersion systems, e.g. gas-containing diagnostic contrast agents.Examples of such ultrasound contrast agents are, for purposes ofillustration and not of limitation, Levovist™, Albunex™, Optison™,Definity™, Imagent™, Sonovue™, Echogen™, Sonogen™ and Sonazoid™.

While the present invention has been discussed in connection with thedelivery of a therapeutic or diagnostic liquid composition, other usesof the invention exist. The agitation mechanism provided by the adapteris also suitable for use in non-medical applications wherein mixing isdesirable, such as e.g. in chemical synthesis.

While the preferred embodiment of the present invention has been shownand described, it will be obvious in the art that changes andmodifications may be made without departing from the teachings of theinvention. The matter set forth in the foregoing description andaccompanying drawings is offered by way of illustration only and not asa limitation. The actual scope of the invention is intended to bedefined in the following claims when viewed in their proper perspectivebased on the prior art.

1. An adapter connectable with an automatic syringe pump and a syringe,the syringe containing contents to be dispensed, said adapter comprisingmeans for agitating the contents of the syringe.
 2. An adapter asclaimed in claim 1, wherein said adapter comprises an adapter bodyreceivable by a syringe-receiving-unit of the syringe pump.
 3. Anadapter as claimed in claim 1 comprising: i) an adapter body receivableby the syringe pump; ii) a syringe retainer for retaining the syringe;and iii) a syringe driver for agitating the contents of the syringe. 4.An adapter as claimed in claim 3 wherein said adapter body furthercomprises an elongate cylindrically shaped portion receivable in thesyringe pump.
 5. An adapter according to claim 3, wherein said syringeretainer further comprises an annular syringe ring defining an insertionaperture, said syringe ring further comprising syringe retaining meansextending about said insertion aperture for engaging and retaining asyringe.
 6. An adapter according to claim 5, wherein said syringeretaining means engages at least one flange transversely projecting fromthe syringe.
 7. An adapter according to claim 5, wherein said syringedriver further comprises a motor and drive means for urging said syringering to rotate about said insertion aperture.
 8. An adapter according toclaim 7, wherein said drive means further comprises a drive beltengaging a moving portion of said motor and said syringe ring.
 9. Anadapter according claim 5 wherein said syringe driver causes saidsyringe ring to reciprocally rotate about said insertion aperture. 10.An adapter as claimed in claim 1, further comprising a portion beingsized and shaped so as to be recognizable by a size-reading unit of thesyringe pump.
 11. An adapter according to claim 3, further comprising asyringe holding arm, wherein said syringe retainer is positioned towardsa free end of said syringe holding arm.
 12. An adapter according toclaim 3, further comprising an elongate guide piston, wherein saidadapter body defines a guide piston opening and an elongate guide pistonpassageway in communication with said guide piston opening for slideablyreceiving said guide piston moving between a first and a secondposition.
 13. An adapter according to claim 12, further comprising anextension arm supported by said guide piston, said extension armincluding a free end in movable spaced registry with said syringeretainer.
 14. An adapter according to claim 13, further comprising adrive rod supported by said extension arm, said drive rod engaging adispensing member of the syringe so as to cause the contents to bedispensed as said drive rod is moved relative to said syringe retainer.15. An adapter according to claim 14, wherein said drive rod isrotateably mounted to said extension arm so as to enable said drive rodto rotate with the syringe.
 16. An adapter according to claim 3, whereinsaid syringe retainer is offset from said adapter body.
 17. An adapterof claim 1, adapted to connect to a syringe such that the adapter bodyand the syringe are positioned substantially in parallel.
 18. An adapterof claim 1, wherein the syringe mounts to one end of said adapter bodysuch that the adapter body and syringe are positioned substantially inline.
 19. Apparatus for administration of an injectable liquidcomprising an automatic syringe pump, a syringe and an adapter asclaimed in claim
 1. 20. Method of administration of an injectable liquidusing an apparatus as claimed in claim
 19. 21. (canceled)